TGF-b EXPRESSION IN RENAL ALLOGRAFT REJECTION AND CYCLOSPORINE TOXICITY

 

BH Ozdemir, AN Haberal, B Demirhan, M Haberal*

Baskent University, Faculty of medicine, Departments of Pathology and General Surgery*, Ankara-Turkey

 

The aim of this study was to assess the distribution of TGF-beta in human renal allograft and to investigate the role of TGF-b in interstitial fibrosis (IF).

The expression of TGF-b and the proportion of macrophages in the interstitium were evaluated immunohistochemically in 64 cases including 5 cases with non-rejected kidneys, 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with CsA toxicity. The follow-up biopsies of all cases with AR and CsA toxicity were also evaluated for the progression of IF.

In the non-rejected group, the glomerular and the interstitial TGF-b expression was totally absent. Tubular TGF-b expression was also negative or only weakly positive in few cases. A significant positive correlation was noted between tubular TGF-b expression and the proportion of macrophage infiltration in cases with AR and CAN (p<0.01). The interstitial TGF-b expression was marked around the macrophage infiltration (p<0.01). There were obvious differences between the cases with AR, CAN and CsA toxicity for the expression of tubular and interstitial TGF-b (p<0.01). Tubular TGF-b expression was marked (grade 3) in 7/26 cases (26.9%) of CAN and 8/15 cases (53.3%) of CsA toxicity. None of cases with AR showed grade 3 TGF-b expression on tubules. A major difference was seen between rejected kidneys and CsA toxicity, in which cases with CsA toxicity exhibited clearly positive tubular TGF-b expression. In striking contrast to other groups, most of the cases with CAN showed TGF-b expression in mesangial cells (p<0.001). In the follow-up biopsies the presence of the IF was found significantly earlier in the cases with AR and CsA toxicity that showed significant TGF-b expression (p<0.01, p<0.05 respectively).

These findings are consisted with the hypothesis that the infiltrating macrophages and CsA may induce the expression of TGF-b. Thereafter TGF-b concomitantly promotes changes such as IF, glomerulosclerosis and vasculopathy associated with CAN.

 

 

TGF-b EXPRESSION IN RENAL ALLOGRAFT REJECTION AND CYCLOSPORINE TOXICITY

BH Ozdemir, AN Haberal, B Demirhan, M Haberal*

Baskent University, Faculty of medicine, Departments of Pathology and General Surgery*, Ankara-Turkey

 

 

 

Correspondence address:

 

B. Handan  Ozdemir MD

Associate Professor

Department of pathology

Baskent University, Faculty of Medicine

Baglar caddesi  194-6

06700 GOP

Ankara, Turkey

Ph:   +90-312-2126591

Fax: +90-312-2127572

e-mail: handan27@hotmail.com